Efficacy and Safety, Long-term Study of Zinc Acetate to Treat Wilson's Disease in Japan.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety, Long-term Study of Zinc Acetate to Treat Wilson's Disease in Japan. (NCT00212355), a na phase 3 study. The primary outcome is Safety and Efficacy.

2. Clinical Question

3. Trial Design

This was a phase 3, open-label clinical trial of zinc acetate for treatment of Wilson's disease in Japan. It used a single-group model: participants received NPC-02, described as zinc acetate, and no concurrent comparator arm is listed. Allocation is recorded as NA and masking as none. Thus, the design does not provide a randomized comparison between zinc acetate and another treatment or control.

The registry lists an enrollment of 37. The study start is recorded as 2005-03, and primary completion as 2008-04. Its status is completed. These dates and status describe the conduct of the study; they do not by themselves indicate whether the intervention changed an outcome.

The primary outcome timeframe is “During study period (up to 96W ).” The registry says the analysis was performed based on the FAS population, but does not define that population or report how participants were assigned to it. Additional eligibility criteria, treatment schedules, follow-up procedures, and details of participant flow are not reported in the registry record.

The lack of a comparator is important when interpreting both safety and efficacy. The study can report events observed among participants in the zinc acetate group, but without a control group it cannot distinguish those events from what might have occurred under another treatment or without the study intervention. The registry record does not report a protocol-level statistical plan or a sample-size justification.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis was performed based on FAS population

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Analysis was performed subjects comprised 37 patients who were found to have Wilson disease through clnical and biochemical tests.

6. Primary Endpoint

The registry lists the primary outcome as Safety and Efficacy, measured over During study period (up to 96W ).

The primary outcome is titled “Safety and Efficacy.” Its description refers to the number of patients with at least one adverse event and to “ALT Change,” and its unit is participants. The timeframe is during the study period, up to 96W. The record identifies the FAS population for the analysis.

A participant count for those experiencing at least one adverse event is a straightforward way to describe how many people had an event during observation. It conveys the reach of reported events across the enrolled group, although a count alone does not describe when events occurred, how long they lasted, or their severity. Those details require separate outcome information.

The outcome description also mentions ALT change, but does not specify the measurement, timing, direction of change, or numerical result. It therefore cannot support a statistical interpretation of ALT. The combined wording leaves the relationship between the adverse-event count and ALT change unclear. The registry record does not report a separate endpoint definition or an efficacy estimate. These omissions limit what can be concluded from the primary outcome entry: the available figures describe adverse-event counts, not a quantified treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a binary outcome type and describes the primary measure as a number of participants with an event. For this kind of measure, the basic information is how many participants were assessed and how many experienced the event. The record supplies at-risk and affected counts for the adverse-event entries, but it does not report an inferential analysis of those counts.

What does a single-group design allow?

In a single-group study, outcomes are described among participants receiving the study intervention. A comparison between randomized groups is not available because the registry lists no comparator and identifies the model as single group. General statistical principle: a treatment effect is a contrast between outcomes under different treatment conditions. Without a concurrent comparison, observed events cannot by themselves show what would have happened to the same population under another condition.

The study is also open-label, with masking listed as none. General statistical principle: when treatment is known, expectations or awareness can influence some measurements and reporting, depending on how an outcome is collected. This concern cannot be quantified from the registry entries, and the record does not describe outcome-assessment procedures.

How should event counts be interpreted?

A count is an observation, not a measure of precision. General statistical principle: uncertainty intervals express a range of values compatible with the observed data under a specified statistical model. They help readers distinguish a relatively precise estimate from one that may be uncertain. No confidence interval or other uncertainty estimate is reported for the adverse-event counts in the registry record. No p-value is reported either; without an analysis and a stated comparison, a p-value would not provide a substitute for the missing control-group contrast.

The record gives a serious-event count and a separate count for other adverse events. The event categories may have distinct registry definitions, but those definitions are not reported. The listed serious-event terms each carry a percentage, but no additional detail is given about timing, recurrence, severity grading, or how terms were selected for listing. The percentages should therefore be read as reported descriptive values rather than as comparative evidence.

What is known about the analysis plan?

The primary analysis is described as based on the FAS population. The registry does not define the FAS, explain how missing observations were handled, or state whether participants were analyzed according to a particular treatment-exposure rule. No analysis method is listed, and the number of analyses is zero. The statistical plan, including any planned adjustment or model specification, is not reported in the registry record.

The record includes a general planning illustration based on a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes effect sizes as stated fractions of an observed effect. For non-time-to-event outcomes, its sample-size convention is participants per arm; for time-to-event outcomes, it is the total number of events. These are planning assumptions, not features of this single-group trial's observed analysis. The registry does not report a trial-specific sample-size justification, and numerical planning results are not reported in the registry record. Such illustrations are not observed power and do not establish that the study was adequately powered.

General statistical principle: over-dispersion occurs when outcome variability exceeds what a chosen statistical model expects. It matters because an unsuitable variance assumption can make uncertainty estimates too narrow or too wide. No dispersion estimate or model is reported for this outcome, and over-dispersion cannot be evaluated from the listed counts alone. The registry also does not report interim analyses, stopping rules, or a prespecified approach to multiplicity.

In practical terms, the available methods information supports only a limited description: the study was single-group, the primary analysis population is called FAS, and adverse-event counts were posted. It does not permit reconstruction of an inferential analysis or assessment of the precision of an efficacy result.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("NPC-02")
n      <- c(37)
events <- c(37)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  NPC-02  37  37  100.0  90.5  100.0  90.6  100.0  90.7  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and zero analyses. The primary outcome entry combines a participant count for at least one adverse event with the phrase “ALT Change,” but it does not explain whether these are separate components, how either was defined in advance, or how they were analyzed. A multiplicity strategy is not reported in the registry record.

General statistical principle: when several outcomes or multiple comparisons are tested, the chance of at least one apparently notable result can increase. A prespecified strategy can address that issue. The posted record does not describe such a strategy, and the absence of listed analyses means there is no reported set of tests from which to assess multiplicity adjustments.

The analysis population is identified as FAS, but its definition is not reported in the registry record. The number of participants included in the analysis, beyond the stated at-risk counts for adverse events, is not separately described. Missing-data rules, the amount and pattern of missing outcome data, and any sensitivity analyses are not reported in the registry record. It is therefore not possible to determine whether all enrolled participants contributed to every outcome or how missing observations may have affected the results.

These gaps do not demonstrate that multiplicity or missing-data methods were absent from the full study conduct; they mean that those methods cannot be evaluated from the registry record. The posted results should be interpreted as descriptive entries, without assuming an unreported adjustment or missing-data procedure.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: depression (2.7%), colitis ulcerative (2.7%), varicella (2.7%), sebaceous naevus (2.7%).

The serious adverse-event entry lists 37 participants at risk and 4 affected in the NPC-02 group. The registry also lists Depression, Colitis ulcerative, Varicella, and Sebaceous naevus as top serious terms, each with a reported value of 2.7%. These are descriptive entries from a single group, not comparisons against a control group.

The separate other adverse-event entry lists 37 at risk and 37 affected. The registry labels this category “other”; its detailed definition is not reported in the registry record. The categories should not be assumed to be mutually exclusive, and the serious-term percentages should not be interpreted as a comparison or as proof of causation.

The death count is not reported in the registry record. A missing death value should not be read as a recorded zero. The registry does not provide event timing, duration, recurrence, or participant-level overlap among event categories. These counts describe what was entered for the study group, but do not establish whether zinc acetate caused an event or how the observed experience compares with another treatment.

13. What the Result Does, and Does Not, Mean

The posted results establish that the registry records adverse events among participants in a single group receiving NPC-02, described as zinc acetate. They include a serious adverse-event count, a separate count for other adverse events, and four listed serious-event terms with reported percentages. The study is marked completed, and its primary outcome timeframe extends during the study period up to 96W.

Those observations do not establish efficacy. Although the primary outcome is titled “Safety and Efficacy,” no numerical efficacy estimate or ALT change is reported. The record also reports no analyses, confidence intervals, or p-values. Without those results, there is no basis in the registry record for quantifying a treatment effect or its precision.

The design also limits causal interpretation. The trial is open-label and single-group, with no comparator listed. General statistical principle: events observed after treatment begins can reflect the intervention, the condition being studied, background risk, or other influences. A comparison group can help distinguish these possibilities; this registry record does not provide one. The adverse-event counts therefore should not be treated as proof that the intervention caused an event, nor as evidence that events would have been more or less common under an alternative.

The study's enrollment and completion status are descriptive details, not evidence that the results are precise or generalizable. Further information about eligibility, participant characteristics, outcome definitions, missing data, and analysis methods is not reported in the registry record. The appropriate reading is limited: the record describes safety events for the study group, while comparative safety and efficacy conclusions remain unresolved by the posted results.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between describing outcomes and estimating comparative effects. Its single-group structure permits reporting events observed among participants, but does not provide a concurrent counterfactual comparison. That distinction matters especially when a registry entry uses broad language such as “Safety and Efficacy”: the title does not replace a defined estimate or an analysis.

The record also shows why outcome definitions and analysis details matter. The primary outcome description combines the number of participants with at least one adverse event and “ALT Change,” yet the numerical ALT result and its measurement details are not reported. Without a clear endpoint definition, it is difficult to determine exactly what a primary result would represent or how to assess its precision.

The available serious-event and other-event counts are useful descriptive information, but the registry provides no uncertainty intervals and no comparator rates. General statistical principle: sample estimates vary, and uncertainty measures help readers assess how much confidence to place in an estimate. Their absence limits precision assessment; it does not turn the observed counts into comparative evidence.

Finally, the record identifies an FAS population while leaving its definition, missing-data approach, and analysis plan unreported. This illustrates why transparent reporting of analysis populations and methods is essential for interpreting clinical-trial results. The study matters statistically not because its posted information settles an efficacy question, but because it demonstrates how design and reporting determine which questions the data can answer.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most important design limitation is the absence of a concurrent comparator. The registry identifies a single-group, open-label study, with allocation listed as NA and masking as none. The observed safety counts therefore cannot be compared with outcomes under another treatment or control condition.

The primary outcome description is not fully clear: it joins the number of participants with at least one adverse event to “ALT Change.” A numerical ALT result, a distinct efficacy outcome, and detailed endpoint definitions are not reported in the registry record. No analyses are listed, so treatment-effect estimates and their uncertainty are unavailable.

The record reports enrollment of 37 and identifies the FAS population, but does not define FAS or give a participant-flow account. Eligibility details, baseline characteristics, missing-data handling, and outcome-assessment procedures are not reported in the registry record. These omissions restrict assessment of who contributed data and how representative the analyzed group may be.

The serious-event and other-event entries are descriptive, and the death count is not reported in the registry record. Detailed event timing, duration, recurrence, and category definitions are also not reported. The statistical plan, sample-size justification, multiplicity approach, and interim analyses are not reported in the registry record. Together, these limits mean that the posted information supports a narrow description of recorded adverse events, not a comprehensive evaluation of comparative safety or efficacy.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety, Long-term Study of Zinc Acetate to Treat Wilson's Disease in Japan. — NCT00212355.
• Registry record last updated 2025-03-05; status last verified 2025-02.
• Results first posted 2014-05-14.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

This completed phase 3 study evaluated zinc acetate, listed as NPC-02, in Japanese participants with Wilson's disease. It was open-label and single-group, with enrollment of 37. The recorded study start was 2005-03, and primary completion was 2008-04.

The primary outcome is titled “Safety and Efficacy” and describes participants with at least one adverse event alongside “ALT Change,” during the study period up to 96W. The analysis population is identified as FAS. The registry lists serious adverse events for 4 of 37 at risk, and other adverse events for 37 of 37 at risk; the death count is not reported in the registry record.

No analyses are listed, and numerical ALT results, comparative estimates, confidence intervals, and the statistical plan are not reported in the registry record. The posted information therefore supports descriptive interpretation of the recorded events, not a comparative treatment-effect conclusion.